Immune checkpoint inhibitor therapy and outcomes from SARS-CoV-2 infection in patients with cancer: a joint analysis of OnCovid and ESMO-CoCARE registries
Authors: Alessio Cortellini, Gino M Dettorre, Urania Dafni, Juan Aguilar-Company, Luis Castelo-Branco, Matteo Lambertini, Spyridon Gennatas, Vasileios Angelis, Ailsa Sita-Lumsden, Jacobo Rogado, Paolo Pedrazzoli, David Viñal, Aleix Prat, Maura Rossi, Rossana Berardi, Teresa Alonso-Gordoa, Salvatore Grisanti, Georgia Dimopoulou, Paola Queirolo, Sylvain Pradervand, Alexia Bertuzzi, Mark Bower, Dirk Arnold, Ramon Salazar, Marco Tucci, Kevin J Harrington, Francesca Mazzoni, Uma Mukherjee, Zoi Tsourti, Olivier Michielin, Fanny Pommeret, Joan Brunet, Bruno Vincenzi, Giuseppe Tonini, Andrea Patriarca, Federica Biello, Marco Krengli, Josep Tabernero, George Pentheroudakis, Alessandra Gennari, Solange Peters, Emanuela Romano, David J Pinato
Journal: Journal for ImmunoTherapy of Cancer (2022)

As management and prevention strategies against COVID-19 evolve, it is still uncertain whether prior exposure to immune checkpoint inhibitors (ICIs) affects COVID-19 severity in patients with cancer. In a joint analysis of ICI recipients from OnCovid (NCT04393974) and European Society for Medical Oncology (ESMO) CoCARE registries, we assessed severity and mortality from SARS-CoV-2 in vaccinated and unvaccinated patients with cancer and explored whether prior immune-related adverse events (irAEs) influenced outcome from COVID-19. The study population consisted of 240 patients diagnosed with COVID-19 between January 2020 and February 2022 exposed to ICI within 3 months prior to COVID-19 diagnosis, with a 30-day case fatality rate (CFR30) of 23.6% (95% CI 17.8 to 30.7%). Overall, 42 (17.5%) were fully vaccinated prior to COVID-19 and experienced decreased CFR30 (4.8% vs 28.1%, p=0.0009), hospitalization rate (27.5% vs 63.2%, p<0.0001), requirement of oxygen therapy (15.8% vs 41.5%, p=0.0030), COVID-19 complication rate (11.9% vs 34.6%, p=0.0040), with a reduced need for COVID-19-specific therapy (26.3% vs 57.9%, p=0.0004) compared with unvaccinated patients. Inverse probability of treatment weighting (IPTW)-fitted multivariable analysis, following a clustered-robust correction for the data source (OnCovid vs ESMO CoCARE), confirmed that vaccinated patients experienced a decreased risk of death at 30 days (adjusted OR, aOR 0.08, 95% CI 0.01 to 0.69).Overall, 38 patients (15.8%) experienced at least one irAE of any grade at any time prior to COVID-19, at a median time of 3.2 months (range 0.13-48.7) from COVID-19 diagnosis. IrAEs occurred independently of baseline characteristics except for primary tumor (p=0.0373) and were associated with a significantly decreased CFR30 (10.8% vs 26.0%, p=0.0462) additionally confirmed by the IPTW-fitted multivariable analysis (aOR 0.47, 95% CI 0.33 to 0.67). Patients who experienced irAEs also presented a higher median absolute lymphocyte count at COVID-19 (1.4 vs 0.8 109 cells/L, p=0.0098). Anti-SARS-CoV-2 vaccination reduces morbidity and mortality from COVID-19 in ICI recipients. History of irAEs might identify patients with pre-existing protection from COVID-19, warranting further investigation of adaptive immune determinants of protection from SARS-CoV-2.